尿酸对大鼠脊髓损伤后保护作用的实验研究

目的 观察尿酸（uric acid，UA）对大鼠脊髓损伤后继发性损害的保护作用. 方法 成年雌性SD大鼠随机分成3组:空白对照组,脊髓损伤组,UA干预组.UA干预组在脊髓损伤造模前1 h和造模成功后4 h经腹腔给予UA 500 mg/kg（用0.9%氯化钠溶液配成悬浮液），空白对照组和脊髓损伤组在同样时点经腹腔注射0.9%氯化钠溶液。在脊髓损伤后8,24,72 h和7 d,对损伤部位脊髓组织丙二醛（MDA）含量，超氧化物歧化酶（SOD）的活性进行检测及病理形态学观察,并采用原位末端标记法（TUNEL）标记凋亡细胞.结果 与脊髓损伤组比较，UA干预组大鼠各时间点损伤部位脊髓组织中MDA含量较脊髓损伤组明显下降(P＜0.05), SOD的活性较脊髓损伤组有明显升高(P＜0.05).病理形态结构改善,神经细胞凋亡减少.结论 UA可以抑制脊髓损伤后自由基的损伤作用,减少神经细胞凋亡,对损伤脊髓组织具有保护作用.     

银杏叶提取物EGb761对大鼠脊髓损伤后的神经保护作用

目的探讨银杏叶提取物EGb761对实验性大鼠脊髓损伤后神经保护的作用及其机制。方法成年雄性SD大鼠132只,体重200～250 g,随机分为正常对照组（N组）、损伤组（T组）、甲基强的松龙治疗组（MP组）和EGb761治疗组（EGb761组）,每组33只。T组、MP组、EGb761组用改良Allen法以25GCF损伤力度致伤大鼠,建立T9脊髓中度损伤模型。术后4、8、24 h每组随机取3只动物切取损伤区1 cm脊髓节段,分别用黄嘌呤氧化酶法和硫代巴比妥酸（TBA）法测定脊髓组织中超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量。分别于术后24 h、3、5、7、14 d处死动物（n=6）,快速取T9节段脊髓,TUNEL法标记细胞凋亡,免疫组化方法检测诱生型一氧化氮合酶（iNOS）的表达。结果术后4、8、24 h EGb761治疗组SOD活性及MDA含量与损伤对照组比较均差异有显著性（P〈0.01）。术后各时相点EGb761治疗组神经细胞凋亡指数和iNOS表达阳性细胞率均低于损伤对照组（P〈0.01或P〈0.05）。结论 EGb761能抑制脊髓损伤后的脂质过氧化反应,减轻神经细胞的凋亡,其机制可能与抑制iNOS表达有关。     

Exendin-4 对大鼠脊髓损伤后氧化应激和神经细胞凋亡的影响

目的研究Exendin-4 对大鼠脊髓损伤后氧化应激和神经细胞凋亡的作用。方法成年雄性SD 大鼠36 只（体质量200~250 g）随机分为3 组（n=12）：假手术组（Sham 组）、单纯脊髓损伤组（SCI 组）、Exendin-4 组（Ex-4 组）。Sham 组只暴露脊髓,不打击;SCI 组和Ex-4 组均采用Allen′s 重物打击法制作脊髓损伤模型;Ex-4 组在脊髓损伤后立即腹腔内注射Exendin-4 溶液,剂量10 μg/只;SCI 组和Sham 组均注射等体积生理盐水。在24 h 后检测各组脊髓组织中丙二醛（MDA）含量和过氧化氢酶（CAT）活性,TUNEL 法检测神经细胞凋亡情况,Western blot 检测 caspase-9 和凋亡诱导因子（AIF）的表达情况。结果与Sham 组相比,SCI 组脊髓组织中的MDA 含量明显增加, caspase-9 和AIF 表达水平明显增加,神经细胞凋亡比例明显升高,CAT 活性明显降低（P < 0.01）。与SCI 组相比, Ex-4 组脊髓组织中MDA 含量明显降低,caspase-9 和AIF 表达水平明显降低,神经细胞凋亡比例明显降低,CAT 活性明显升高（P < 0.01）。结论大鼠脊髓损伤后,Exendin-4 可通过减轻氧化损伤抑制神经细胞凋亡。     

依达拉奉促进大鼠脊髓损伤神经功能恢复作用研究

目的 观察依达拉奉对急性脊髓损伤大鼠神经功能评分的影响，探讨依达拉奉促进大鼠脊髓损伤神经功能恢复的作用。方法 采用改良Allen法制作SD大鼠脊髓中度损伤模型，将模型鼠随机分为实验组和对照组各16只。实验组按3 mg·kg^-1的剂量将依达拉奉用0.9%氯化钠溶液稀释后，每隔12 h腹腔注射1次，给药时间为30 min，共14 d。对照组采用同样方式给予0.9%氯化钠溶液。比较实验开始后不同时间大鼠斜板试验、神经功能评分变化。结果 从伤后2周和3周起，实验组的斜板最大角度和神经功能评分分别与对照组比较均差异有极显著性（均P＜0.01）。结论 依达拉奉对大鼠脊髓损伤神经功能的恢复具有促进作用。     

依达拉奉对急性脊髓损伤后的大鼠神经组织氧化损害保护作

目的 探讨依达拉奉对急性脊髓损伤后的大鼠神经组织保护机制.方法 90只SD大鼠随机分为假手术组(n=30),ASCI对照组(n=30)和依达拉奉干预组(n=30),采用改良的Allen法,制成中度脊髓损伤大鼠模型;每组分别于6h、12h、24h、48h、72h5个时点,每个时点6只大鼠,检测各组各时点血清及脊髓中的NO、SOD、MDA的含量及脊髓组织含水量变化;TUNEL法检测72h后各组脊髓中的神经细胞凋亡及Caspase-3mRNA阳性细胞.结果 对照组各时点SOD活性明显低于假手术组,而NO、MDA含量明显高于假手术组,对照组各时点含水量与SOD活性呈明显负相关,与MDA含量呈明显正相关,依达拉奉干预组各时点SOD活性明显高于对照组,而NO、MDA含量明显低于对照组,依达拉奉干预组各时点含水量与SOD活性呈明显负相关,与MDA含量呈明显正相关,假手术组脊髓中无或偶见凋亡细胞及阳性染色细胞,对照组可见大量凋亡细胞及阳性染色细胞,依达拉奉干预组凋亡细胞及阳性染色细胞数量较对照组明显减少.结论 依达拉奉通过有效地清除氧自由基,可明显抑制急性脊髓损伤后的脂质过氧化反应及降低神经细胞的凋亡,从而达到保护其神经组织的作用.     

右丙亚胺对表柔比星致大鼠心肌损伤的保护作用及机制研究

目的探讨右丙亚胺对表柔比星致大鼠心肌损伤的保护作用及其机制,为临床用药提供实验依据。方法将35只SD大鼠随机分为5组：正常对照组、模型组（表柔比星＋生理盐水）、表柔比星＋低剂量右丙亚胺组（DEX1）、表柔比星＋中剂量右丙亚胺组（DEX2）、表柔比星＋高剂量右丙亚胺组（DEX3）,给药后检测各组大鼠心肌组织微量丙二醛（MDA）含量、总超氧化物歧化酶（T-SOD）活性和血浆乳酸脱氢酶（LDH）水平并观察心肌细胞凋亡的情况。结果与正常对照组比较,模型组大鼠心肌组织的SOD活性明显降低,MDA含量、血浆LDH含量和心肌细胞凋亡指数均明显升高（P〈0.01）;而与模型组比较,用右丙亚胺处理的各组大鼠心肌组织SOD活性明显升高,心肌组织MDA含量、心肌细胞凋亡指数及血浆LDH含量均显著降低（P〈0.01或P〈0.05）。结论右丙亚胺能减少表柔比星所致的心肌细胞凋亡,可能与其降低氧自由基的产生和脂质过氧化产物含量有关。     

和胃冲剂对大鼠急性胃黏膜损伤的保护作用

目的：观察中药复方和胃冲剂对大鼠急性胃黏膜损伤的保护作用。方法：将40只健康♂性Spaque-Dawley大鼠随机分为5组：正常对照纽、模型对照组、和胃冲剂低、中、高剂量组，采用无水乙醇诱导大鼠急性胃黏膜损伤，分别测定各组大鼠的胃黏膜损伤指数、血浆超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量，并在光镜下观察胃黏膜病理学改变。结果：和胃冲剂各剂量组的损伤指数较模型对照组显著降低（P〈0．01），且呈剂量依赖性；血浆中SOD活性显著升高，MDA含量下降，黏膜损伤程度明显减轻。结论：和胃冲剂对无水乙醇诱导的急性胃黏膜损伤有明显的保护作用，其机制可能与抗氧化作用有关。     

参奇颗粒对心肌缺血再灌注损伤的保护作用

目的:研究参奇颗粒对心肌缺血再灌注损伤的保护作用以及作用机制.方法:采用冠脉结扎手术建立心肌缺血再灌注损伤模型,通过对大鼠血清中GSH-PX、SOD、MDA活性的影响以及对大鼠心肌梗死面积(MIS)和心肌细胞凋亡率的影响的测定来考察参奇颗粒对大鼠心肌缺血再灌注损伤的保护作用.结果:与假手术组比较,模型组能显著升高大鼠心肌血清中GSH-PX、SOD活性和心肌MPO活性(P＜0.05,P＜0.01,P＜0.01),能降低大鼠血清中MDA活性(P＜0.05),与模型组比较,参奇颗粒低、中、高剂量组均能升高大鼠血清中GSH-PX活性、SOD活性(P＜0.05,P＜0.01);参奇颗粒高、中、低剂量组均能降低大鼠血清中MDA活性(P＜0.01);参奇颗粒低、中、高剂量组能够降低大鼠心肌MPO活性(P＜0.05,P＜0.01);给药组低、中、高剂量组均能够降低心肌梗死程度差异显著(P＜0.05,P＜0.01),心肌细胞凋亡指数具有显著差异(P＜0.01),起到保护心肌的作用,效果呈现剂量依赖性.结论:参奇颗粒对大鼠心肌缺血再灌注损伤及作用机制研究具有一定的作用.     

依达拉奉预处理对心肌缺血-再灌注损伤大鼠的保护作用

目的 探讨依达拉奉预处理对大鼠心肌缺血-再灌注损伤（MIRI）的保护作用及其可能机制. 方法 MIRI模型制备完成后,30只SD大鼠随即分为假手术组（0.9%氯化钠溶液预处理）、缺血-再灌注组（0.9%氯化钠溶液预处理）、依达拉奉组（依达拉奉预处理）. 假手术组开胸后只穿线不结扎,缺血-再灌注组和依达拉奉组均结扎左冠状动脉前降支,用止血钳固定持续缺血30 min,放松止血钳120 min. 测定血清超氧化物歧化酶（SOD）活性和丙二醛（MDA）、心肌型肌酸激酶同工酶（CK-MB）、肿瘤坏死因子-α（TNF-α）含量,以及心肌坏死组织质量. 结果 与假手术组比较,缺血-再灌注组的SOD活性明显降低,MDA、CK-MB、TNF-α含量明显升高,其差异均有极显著性（P＜0.01）;与缺血-再灌注组比较,依达拉奉组SOD活性明显升高,MDA、CK-MB、TNF-α含量明显降低,其差异有极显著性（P＜0.01）;与缺血-再灌注组比较,依达拉奉组AAR、IS/AAR明显降低,差异有显著性（P＜0.05）. 结论 依达拉奉预处理对MIRI具有保护作用,其可能的机制是提高SOD活性,减轻氧自由基对细胞膜的损伤.     

依达拉奉对慢性低氧高二氧化碳大鼠 学习记忆能力的影响

［摘要］目的探讨依达拉奉对慢性低氧（O2）高二氧化碳（CO2）大鼠学习记忆能力的影响及其作用机制。方法雄性SD大鼠24只，随机分为对照组、低O2高CO2 4周组（模型组）、低O2高CO24周＋依达拉奉治疗组（依达拉奉组），每组8只。用Morris水迷宫检测大鼠学习记忆能力并测定海马组织中超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量。结果与对照组相比，模型组逃避潜伏期明显延长，且SOD活性明显降低（P＜0.01），MDA含量明显升高（P＜0.01）。与模型组相比，依达拉奉组大鼠逃避潜伏期明显缩短，且SOD活性明显升高（P＜0.01），MDA含量明显降低（P＜0.01）。结论依达拉奉可改善慢性低O2高CO2大鼠学习记忆能力，其作用机制与升高SOD活性和降低MDA含量有关。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

---

Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.